Monday, September 16, 2013

Make you choice - cholesterol and regular sugar (left), or fat free and fructose-laden? In the end it all may not even matter.

When I stumbled upon a recent study from the University of Colorado a few days ago, my first thought was: Oh my! That sounds familiar. And indeed, if you know anything about the "cholesterol conundrum" you will probably feel reminded of the disconnect between cholesterol intake, cholesterol levels in the blood and cholesterol-related increases in cardiovascular disease risk - don't forget that this is still an issue, although it may neither be your dietary cholesterol or your total cholesterol levels that mediate the risk increases.

Looks like you cannot pick your poison, because whatever you chose, your body will produce what it considers fitting from it

According to the said study from the University of Colorado it does in fact seem that our current favorite villain, namely fructose, has more in common with its predecessor on the throne of "avoid at all costs nutritional evils", i.e. cholesterol, than we have previously thought.

Surprise! Some of you may have heard about it for the first time 8 days ago in the first serving of insulin-sensitizing supplements, here at the SuppVersity: Amla aka Emblica officinalis is a natural aldose reductase inhibitor (Pupalla. 2012) and would thus be qualified to keep the negative side effects of endogenous fructose production in check!

"Many high glycaemic foods also contain fructose. For
instance, sucrose is a disaccharide of glucose and fructose, and
high-fructose corn syrup is a mixture of glucose and fructose,
raising the question of whether fructose is responsible for the
effects of high glycaemic foods to increase the risk for metabolic
syndrome. To further complicate this issue, fructose can be
generated endogenously via the polyol pathway from glucose.
Specifically, aldose reductase (AR) metabolizes glucose to sorbitol,
which can then be converted to fructose by sorbitol
dehydrogenase.

Thus, if AR were highly expressed or activated
in the liver, some of the glucose absorbed might be converted to
fructose, and hence possibly provide a mechanism for inducing
features of the metabolic syndrome."

To render this a little more straight forward, let's get back to our cholesterol analogy: We know (or should know) that part of the reason that dietary cholesterol is not a danger / problem for us is a simple consequence of the fact that most of the cholesterol that's floating around in our blood is actually produced directly within our bodies. And for cholesterol the rule of thumb is: The less cholesterol we eat, the more we will be producing ourselves.

Do we sugar- / fruit-coat ourselves?

For fructose this should actually be different. After all, fructose is not of similar physiologic importance to us as cholesterol the "fatty acid shuttle" and steroid precursor. Still, necessary or not, at least the results of the study at hand appear to suggest that the mammalian body appears to like his fructose so much that it will just produce it on its own, even when the diet is fructose free.

Unforuntately, the consequences Lenaspa et al. observed, when they kept 4 groups of rodents (wild-type and fructokinase knockout (KO) mice, who cannot produce fructose from glucose) on diets with or without glucose (10% (wt/vol))
in the drinking water and compared the body compositional changes of these mice to a control group pm regular chow (containing 60%
carbohydrate and no fructose), appear to suggest that this is exactly as bad as guzzling fructose corn syrup all day.

Figure 1 : When the aldose reductase enzyme is deactivated mice will gain significantly less weight and avoid both insulin resistance and NAFLD despite being on a high glucose (no sugar) diet (Lanaspa. 2013)

In fact, the absence of the enzymes that are necessary to do the conversion of glucose to fructose did not just lead to a major and significant reduction in weight gain, it also blunted the typical pro-non-fatty liver disease effects of high sugar diets and kept the insulin sensitivity of the knockout mice in the glucose group in check.

"These studies suggest that under certain conditions glucose may induce metabolic syndrome in mice via an AR [=fructose production via aldose reductase], fructose-dependent pathway. Whether this is occurring in humans ingesting high glycaemic foods remains to be determined. However, as in mice, AR can be activated in humans by a number of ways, including by high glucose concentrations. Total parenteral nutrition, in which a 35% glucose solution is provided
by the vein, is associated with the development of fatty liver, andexperimental studies have shown that it is mediated by the glucose component of the infused fluids

Soft drinks containing high-fructose corn syrup also deliver markedly high-glucose solutions (4–6%) to the gut, and sucrose-containing soft drinks provide similar amounts of glucose after the sucrose is degraded in the intestine." (Lanaspa. 2013)

With these new results it becomes even more obvious why HFCS which is actually a mixture of glucose and fructose is particularly nasty. It will not only increase the absorption of fructose (see Figure 2), but also provide our bodies with the necessary substrate to top an already overabundant fructose intake off with endogenously fructose to create something even I, as an outspoken critic of the "fructose hypothesis of obesity" would say is part of the perfect obesogenic storm and could easily explain why soft drink intake is so closely associated with an increased risk for obesity, fatty liver and insulin resistance.

Suggested read on the never-ending debate on the "fundamental difference" between glucose and fructose: "Glucose vs. Fructose and Their Effects on Glucose, Insulin & Fat Oxidation" | read more

Bottom line: No, the study at hand does not imply that HFCS is harmless (on the contrary it adds another reason it's poison), but it should remind all of us that an exuberant (but not an appropriate) glucose intake is not necessarily causing less damage than fructose. Consumed in high enough amounts it's going to set the fructose production machinery of our body in gear and will thus yield very similar metabolic problems as fructose itself, the current scape-goat for "all things metabolic syndrome".

If you want to make absolute sure you really mess yourself up, I do however strongly advice you add some saturated fats, preferentially palmitic acid, to maximize insulin resistance and make sure the glucose cannot be taken up by your muscle before it can either harm you directly, or after being converted to fuctose or triglycerides.

What? Oh yeah, you're right! That's what 90% of our fellow Westerners do. Eating a high fat, high carb diet and sitting around all day... well, I guess it's thus not the fructose from the one apple they consume per months that's to blame for their misery, is it?References:

Ushijima K, Riby JE, Fujisawa T, Kretchmer N. Absorption of fructose by isolated small intestine of rats is via a specific saturable carrier in the absence of glucose and by the disaccharidase-related transport system in the presence of glucose. J Nutr. 1995 Aug;125(8):2156-64.

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The information provided on this website is for informational purposes only. It is by no means intended as professional medical advice. Do not use any of the agents or freely available dietary supplements mentioned on this website without further consultation with your medical practitioner.